How Does HIV Cause AIDS?

diagram of a human immunodeficiency virus

Last week, we gave a general background of human immunodeficiency virus (HIV), the virus that causes AIDS by destroying the immune system. But how is HIV able to disable our immune systems so effectively, anyway? The answer lies in its structure.

HIV, just like any other virus, is made up of a tiny capsule with a small piece of genetic code inside. While most viruses we’re familiar with store their genes on a molecule called DNA, HIV contains two pieces of RNA, which is another type of gene-storing molecule. The HIV capsules also contain an enzyme called transcriptase, which “translates” the RNA into a strand of DNA that our cells can read. Our cells are then tricked into reading this DNA and producing more copies of the virus — which are then released from the host cell, at which point they are free to infect other cells. In this manner, an HIV infection slowly grows.

HIV targets our immune systems, the very mechanism that evolved to keep us safe from pathogens.

When a virus is introduced into a host’s body, immune cells pick it up and carry it to the lymphoid organs — which are a sort of meeting place for other types of immune cells, including CD4+ T helper cells (also called helper T cells). Helper T cells enlist the help of other immune cells, called killer T cells, which destroy cells infected with viruses. Helper T cells also activate the production of antibodies, molecules that are specialized to attach to a specific pathogen so that it can be destroyed. Normally, this is where the virus meets its end. Unfortunately, HIV is different from run-of-the-mill viruses in that it is specialized to invade helper T cells. Now, instead of coordinating an attack against HIV, the helper T cells have been hijacked — converted into factories for the production of yet more HIV.

This illustration shows how HIV uses a co-receptor, such as CCR5, to gain entry into a host cell. Image: National Institute of Allergy and Infectious Diseases

This illustration shows how HIV attaches to a receptor to gain entry into an immune cell. Image: National Institute of Allergy and Infectious Diseases

HIV invades a helper T cell by attaching to its surface, after which the virus fuses to the cell. A hole forms, allowing the RNA to move from the capsule into the cell’s interior. HIV’s genetic code is integrated with the host’s cellular DNA. The cell might start producing more copies of HIV, or the infection might enter into a period of dormancy. While an HIV-infected cell lies dormant, it cannot be detected by other immune cells, allowing a “reservoir” of HIV to persist in the host’s body.

Another way HIV can outsmart the immune system lies in its especially high mutation rate, which results from its need to translate its RNA into DNA. Unlike DNA viruses, HIV lacks a “proofreading” capability, which means these mutations aren’t ever corrected. These aspects of HIV’s genetic structure make it highly unstable, mutating so rapidly that a person in the end stage of an HIV infection might be home to 100 million genetically distinct variations of the virus. When the virus keeps changing its appearance, it can be even more difficult for the immune system to mount a defense against it.

There are three stages of an HIV infection:

  1. Symptoms are mild (e.g., swollen lymph nodes) or absent altogether. In just a couple of weeks, billions of helper T cells are infected, but viral load is quickly reduced by the immune system, which at this point is not fully compromised. At around three months, “seroconversion” takes place, which means that detectable antibodies appear in the bloodstream.
  2. HIV levels stabilize in the bloodstream, although levels of helper T cells steadily decline. Some new HIV particles are released by infected cells, but many remain dormant. At this point, there are early indications of a failing immune system: Persistent yeast infections, diarrhea, shingles, and oral leukoplakia (white patches inside of the mouth) are common symptoms.
  3. When helper T cell counts fall below 200 cells per microliter of blood, an HIV infection is considered to have advanced to AIDS. At this point, serious infections and cancers can move in — common ones include tuberculosis, Pneumocystis pneumonia, toxoplasmosis of the brain, and Kaposi’s sarcoma. Production of new HIV particles rises as 100 billion of them are produced daily, overwhelming the body’s defenses. When more helper T cells are destroyed than created, the body is no longer able to compensate for the loss of immune cells.

Left untreated, a typical HIV infection runs its course over a decade or so. (Some people, called long-term nonprogressors, are able to remain symptom-free and with stable helper T cell levels for much longer, possibly surviving for 25 years or more.) Luckily, antiretroviral medications have dramatically increased survival and quality of life by delaying the onset of AIDS. There are drugs that target the enzyme that “translates” HIV’s RNA into DNA; drugs that inhibit the ability of new HIV particles to assemble themselves; drugs that disrupt the fusion process between an HIV particle and a host cell; drugs that make it difficult for the viral DNA to integrate with the host cell’s DNA; and more.

A combination of these drugs — up to 40 pills a day — can attack the virus from so many directions that its wily ways are severely hampered. Drug resistance can evolve, which makes the complex schedule important to follow carefully. These medications are nowhere close to a cure, and they have side effects, but their pros vastly outweigh the cons as they have led to lower HIV transmission rates and a delayed onset of symptoms.

The best thing a sexually active person can do to avoid an HIV infection is to practice safer sex — using condoms, female condoms, and dental dams. HIV testing is also important — frequent screening can allow someone to start treatment early in the infection if he or she tests positive. You can learn about safer sex techniques and receive HIV screening at any Planned Parenthood health center.